Structured Interview For Psychosis-Risk Syndromes Research Articles

Identification of youth at clinical high-risk for psychosis: A community-based study from India.

A two-stage process, wherein self-report screening precedes the structured interview, is suggested for identifying individuals at clinical high-risk for psychosis (CHR-P) in community samples. Aim of this study was to screen a community youth sample from India for CHR-P using the two-stage method. Specific objectives were to assess concordant validity of the self-report measure and predictive validity of the two-stage method. Based on probability sampling, 2025 youth aged 15-24 years were recruited from one rural and one urban area of Telangana, a Telugu-speaking state in India. Telugu version of the PRIME Screen-Revised (PS-R) and structured interview for psychosis-risk syndromes (SIPS) were used. CHR-P positive and negative cohorts were followed-up for transition to psychosis at 3-monthly intervals. One hundred ten individuals screened positive on PS-R. SIPS conducted on 67 out of 110 individuals confirmed 62 (92.54%) to be CHR-P positive. PS-R showed 98.41% sensitivity and 90.74% specificity. Among CHR-P positive, three participants transitioned to psychosis in 15 months. The hazard ratio for psychosis transition was 11.4. Screening accuracy of PS-R in the community youth sample in Telangana is optimum. The hazard ratio for psychosis transition in the community identified CHR-P indicates good predictive validity for the two-stage method.

The Complex Latent Structure of Attenuated Psychotic Symptoms: Hierarchical and Bifactor Models of SIPS Symptoms Replicated in Two Large Samples at Clinical High Risk for Psychosis.

The Structured Interview for Psychosis-Risk Syndromes (SIPS) and other assessments of psychosis risk define clinical high risk for psychosis (CHR) by the presence of attenuated psychotic symptoms. Despite extensive research on attenuated psychotic symptoms, substantial questions remain about their internal psychometric structure and relationships to comorbid non-psychotic symptoms. Hierarchical and bifactor models were developed for the SIPS in a large CHR sample (NAPLS-3, N = 787) and confirmed through preregistered replication in an independent sample (NAPLS-2, N = 1043). Criterion validity was tested through relationships with CHR status, comorbid symptoms/diagnoses, functional impairment, demographics, neurocognition, and conversion to psychotic disorders. Most variance in SIPS items (75%-77%) was attributable to a general factor. Hierarchical and bifactor models included a general factor and five specific/lower-order factors (positive symptoms, eccentricity, avolition, lack of emotion, and deteriorated thought process). CHR participants were elevated on the general factor and the positive symptoms factor. The general factor was associated with depressive symptoms; functional impairment; and mood, anxiety, and schizotypal personality diagnoses. The general factor was the best predictor of psychotic disorders (d ≥ 0.50). Positive symptoms and eccentricity had specific effects on conversion outcomes. The deteriorated thought process was least meaningful/replicable. Attenuated psychotic symptoms, measured by the SIPS, have a complex hierarchical structure with a strong general factor. The general factor relates to internalizing symptoms and functional impairment, emphasizing the roles of general psychopathological distress/impairment in psychosis risk. Shared symptom variance complicates the interpretation of raw symptom scores. Broad transdiagnostic assessment is warranted to model psychosis risk accurately.

Psychosis spectrum symptoms among individuals with schizophrenia-associated copy number variants and evidence of cerebellar correlates of symptom severity

The 3q29 deletion (3q29Del) is a copy number variant (CNV) with one of the highest effect sizes for psychosis-risk (>40-fold). Systematic research offers avenues for elucidating mechanism; however, compared to CNVs like 22q11.2Del, 3q29Del remains understudied. Emerging findings indicate that posterior fossa abnormalities are common among carriers, but their clinical relevance is unclear. We report the first in-depth evaluation of psychotic symptoms in participants with 3q29Del (N=23), using the Structured Interview for Psychosis-Risk Syndromes, and compare this profile to 22q11.2Del (N=31) and healthy controls (N=279). We also explore correlations between psychotic symptoms and posterior fossa abnormalities. Cumulatively, 48% of the 3q29Del sample exhibited a psychotic disorder or attenuated positive symptoms, with a subset meeting criteria for clinical high-risk. 3q29Del had more severe ratings than controls on all domains and only exhibited less severe ratings than 22q11.2Del in negative symptoms; ratings demonstrated select sex differences but no domain-wise correlations with IQ. An inverse relationship was identified between positive symptoms and cerebellar cortex volume in 3q29Del, documenting the first clinically-relevant neuroanatomical connection in this syndrome. Our findings characterize the profile of psychotic symptoms in the largest 3q29Del sample reported to date, contrast with another high-impact CNV, and highlight cerebellar involvement in psychosis-risk.

Ultra-high risk for psychosis stigma: an updated Systematic Review.

To clarify if stigma associated with schizophrenia has also been directed towards the ultra-high risk for psychosis (UHR) population, the present review aimed at synthetizing the existing literature to update and extend our understanding on the topic. A systematic PRISMA-compliant review was performed in PubMed, Embase, Cochrane and Web of Science for articles published until 30/04/2023, using a combination of search terms describing the at-risk mental states for psychosis and stigma and correlated terms. Thirty-eight studies were included. Twenty-nine addressed UHR individuals directly, and 9 conducted interviews with non-patients regarding UHR. A total of 2560 UHR individuals were assessed; mean sample size was of 88.3 participants. Most of the studies were quantitative non-randomized/observational with young adults, 71.4% used SIPS (Structured Interview for Psychosis-risk Syndromes) and 25.0% used CAARMS (Comprehensive Assessment of At-Risk Mental States). Overall, the summarized studies have mainly involved individuals already attending UHR clinics from Western and high income countries. Studies can be grouped into five forms of stigma, among which the most frequently explored was perceived public stigma, followed by public stigma, self-stigma/internalized stigma, stigma stress and associative stigma. The main study design was quantitative nonrandomized, with only one interventional study. Most of the results confirmed the presence of stigma toward UHR individuals and findings provide additional support to the fact that stigma seems to be present since the very early stages of the disease. There is still a paucity of research and knowledge gaps about UHR-related stigma. Nevertheless, results suggest the presence of stigma toward UHR individuals, supporting the fact that stigma is present since the early stages of psychosis.

Generalizability and Out-of-Sample Predictive Ability of Associations Between Neuromelanin-Sensitive Magnetic Resonance Imaging and Psychosis in Antipsychotic-Free Individuals

The link between psychosis and dopaminergic dysfunction is established, but no generalizable biomarkers with clear potential for clinical adoption exist. To replicate previous findings relating neuromelanin-sensitive magnetic resonance imaging (NM-MRI), a proxy measure of dopamine function, to psychosis severity in antipsychotic-free individuals in the psychosis spectrum and to evaluate the out-of-sample predictive ability of NM-MRI for psychosis severity. This cross-sectional study recruited participants from 2019 to 2023 in the New York City area (main samples) and Mexico City area (external validation sample). The main samples consisted of 42 antipsychotic-free patients with schizophrenia, 53 antipsychotic-free individuals at clinical high risk for psychosis (CHR), and 52 matched healthy controls. An external validation sample consisted of 16 antipsychotic-naive patients with schizophrenia. NM-MRI contrast within a subregion of the substantia nigra previously linked to psychosis severity (a priori psychosis region of interest [ROI]) and psychosis severity measured using the Positive and Negative Syndrome Scale (PANSS) in schizophrenia and the Structured Interview for Psychosis-Risk Syndromes (SIPS) in CHR. The cross-validated performance of linear support vector regression to predict psychosis severity across schizophrenia and CHR was assessed, and a final trained model was tested on the external validation sample. Of the 163 included participants, 76 (46.6%) were female, and the mean (SD) age was 29.2 (10.4) years. In the schizophrenia sample, higher PANSS positive total scores correlated with higher mean NM-MRI contrast in the psychosis ROI (t37 = 2.24, P = .03; partial r = 0.35; 95% CI, 0.05 to 0.55). In the CHR sample, no significant association was found between higher SIPS positive total score and NM-MRI contrast in the psychosis ROI (t48 = -0.55, P = .68; partial r = -0.08; 95% CI, -0.36 to 0.23). The 10-fold cross-validated prediction accuracy of psychosis severity was above chance in held-out test data (mean r = 0.305, P = .01; mean root-mean-square error [RMSE] = 1.001, P = .005). External validation prediction accuracy was also above chance (r = 0.422, P = .046; RMSE = 0.882, P = .047). This study provided a direct ROI-based replication of the in-sample association between NM-MRI contrast and psychosis severity in antipsychotic-free patients with schizophrenia. In turn, it failed to replicate such association in CHR individuals. Most critically, cross-validated machine-learning analyses provided a proof-of-concept demonstration that NM-MRI patterns can be used to predict psychosis severity in new data, suggesting potential for developing clinically useful tools.

The 68 symptoms of the clinical high risk for psychosis: Low similarity among fourteen screening questionnaires

The Clinical High Risk for psychosis (CHR) is a heterogeneous condition with multiple symptoms. CHR screening is challenging in routine care, as a wide variety of questionnaires exists. We propose to explore the extent to which these questionnaires differ or overlap in item content. We performed a systematic and quantitative analysis of item content in a set of widely-used CHR screening questionnaires. Items were extracted from questionnaires and reworded according to the Structured Interview for Psychosis-Risk Syndromes (SIPS). Then, symptoms were generated from individual items. The Jaccard Index was calculated to assess content overlap. The 14 analysed questionnaires were composed of 347 items, from which 198 symptoms were generated and, in turn, collapsed into 68 distinct symptoms. Positive symptoms were the most commonly represented. The overall overlap across questionnaires showed weak similarity (Jaccard = 0.19±0.50). CHR screening questionnaires might evaluate the same broad clinical construct, but have different scopes within that construct, and may be more or less comprehensive than one another. Clinicians and researchers should be mindful of the specific features of each instrument for optimal CHR screening.

Development of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS.

To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses.

Associations between acute and chronic lifetime stressors and psychosis-risk symptoms in individuals with 22q11.2 copy number variants

The 22q11.2 deletion (22q11Del) is among the strongest known genetic risk factors for psychosis. Stress, a known risk factor for psychosis in the general population, has seldom been studied in 22q11Del. We investigated how lifetime stressors related to symptomatic outcomes in patients with 22q11Del. We also explored this association in individuals with 22q11.2 duplications (22q11Dup), which may be potentially protective against psychosis. One hundred individuals (46 with 22q11Del, 30 with 22q11Dup, and 24 healthy controls; Mage = 17.30 years±10.15) were included. Logistic models were used to examine cross-sectional associations between lifetime acute and chronic stressors (severity and count) and the presence (score ⩾3) of positive, negative, and general symptoms, assessed via the Structured Interview for Psychosis-risk Syndromes (SIPS). The 22q11Dup group reported the greatest number and severity of acute lifetime stressors, but did not differ from 22q11Del in chronic stressor count or severity. Lifetime chronic and acute stressors were uniquely associated with positive symptoms in 22q11Del (chronic count: odds ratio [OR] = 2.35, p = 0.02; chronic severity: OR = 1.88, p = 0.03; acute count: OR = 1.78, p = 0.03), but not with negative or general symptoms (ps > 0.05). Findings suggest that stress may play a role in psychotic symptoms in 22q1Del, while the 22q11Dup CNV appears protective against psychotic symptoms despite higher rates of stressors. Interventions that mitigate effects of stressors in 22qDel may reduce the odds of psychosis in this group. Prospective longitudinal research is needed to replicate these findings.

Symptoms of Attenuated Psychosis Syndrome in Relatives of Clinical High-Risk Youth: Preliminary Evidence.

Attenuated Psychosis Syndrome (APS) impacts functioning and predicts increased risk of psychosis. Risk for developing APS itself has received minimal attention. Knowledge of familial and environmental contributions to APS symptoms would advance understanding of APS and risk for psychosis. As an initial step, this report presents the first data on APS symptoms in family members of APS patients. This study utilized a discordant sibling-pair family study design. The Structured Interview for Psychosis-risk Syndromes (SIPS) was administered to 17 APS probands and 26 non-APS biological siblings. Probands and siblings were compared on positive, negative, disorganized, and general SIPS symptom scales and factors derived from those scales. There was significantly greater symptom severity in probands compared to siblings on nine of 19 SIPS scales. Negative/anxiety, functioning, and positive symptom factors were identified. Probands showed significantly greater severity than siblings on the negative/anxiety and positive factors. Elevated pathology on the negative/anxiety factor best differentiated between probands and siblings, over and above the contribution of the positive factor. No difference was found for the functioning factor. Results support the importance of non-familial effects on risk for APS and suggest differences in familial contribution to APS symptoms. Understanding the relative contribution of familial and environmental effects on APS symptoms may reveal important differences among APS patients, with implications for risk characterization, symptom course, and treatment selection.

The association between mental health stigma and face emotion recognition in individuals at risk for psychosis.

Self-stigma has been associated with reduced accuracy of face emotion recognition in individuals at clinical high risk for psychosis (CHR). Stigma may also relate to slowing of performance during cognitive tasks for which a negative stereotype is relevant. This study aimed to investigate the association of mental illness stigma with face emotion recognition among CHR individuals. Participants were 143 CHR individuals identified using the Structured Interview for Psychosis-Risk Syndromes (SIPS). Face emotion recognition was assessed using the Penn Emotion Recognition Task (ER-40). Stigma was assessed using discrimination, stereotype awareness, and stereotype agreement subscales of the Mental Health Attitudes Interview for CHR. We tested associations of ER-40 accuracy and response times with these stigma variables, including the role of clinical and demographic factors. Racial/ethnic minoritized participants had higher attenuated positive symptoms than non-minoritized participants. Longer ER-40 response times were correlated with greater stereotype agreement (r=.17, p=.045) and discrimination (r=.22, p=.012). A regression model predicting ER-40 response times revealed an interaction of stereotype agreement with minoritized status (p=.008), with slower response times for minoritized participants as stereotype agreement increased. Greater disorganized symptoms and male gender also predicted longer response times. ER-40 accuracy was not associated with stigma. Overall, minoritized CHR individuals with greater internalized stigma took longer to identify face emotions. Future research is needed to assess whether slower response times are specific to social cues, and if internalized stigma interferes with performance in real-world social situations. Reducing stigma may be an important target for interventions that aim to improve social skills.

Harmonizing the structured interview for psychosis-risk syndromes (SIPS) and the comprehensive assessment of at-risk mental states (CAARMS): An initial approach.

The two most used semi-structured psychometric instruments that define criteria for being at clinical high risk (CHR) for psychosis are the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Structured Interview for Psychosis-Risk Syndromes (SIPS). Although very similar there are important differences between these two measures. Developing harmonized psychometric criteria for defining CHR and associated outcomes would be beneficial for future research. This article describes the first step in this process by reporting on a NIMH workshop held in Washington DC, in February 2019 that was attended by experts in the field. The aim of this workshop was to examine the similarities and differences between the two measures and consider how the harmonization process could proceed.

The Mini-SIPS: development of a brief clinical structured interview guide to diagnosing DSM-5 Attenuated Psychosis Syndrome and training outcomes

ObjectiveThe Mini-SIPS, a condensed version of the Structured Interview for Psychosis-Risk Syndromes (SIPS), is intended to efficiently identify for clinicians the minimum information needed to support a DSM-5 Attenuated Psychosis Syndrome (APS) diagnosis.MethodsThe instrument and the DSM-5 criteria are accessible through the online training program.ResultsMost individuals (67.5%) in the first 212 to complete the training program indicated an intended use of the Mini-SIPS exclusively for clinical purposes. Performance on the post-training quiz was excellent for those with and without prior training in structured diagnostic interviewing.ConclusionThe Mini-SIPS, and accompanying training program, are offered as public-domain clinical resources to the mental health community.

Do the Components of Attenuated Positive Symptoms Truly Represent One Construct?

Psychosis-risk inventories, like the Structured Interview for Psychosis-Risk Syndromes (SIPS), utilize symptom components and coalesce the information into a single-severity rating. These components include frequency, duration, in-the-moment conviction, retrospective insight, distress, and effect on social/role functioning. While combining components distills a great deal of important information into one practical symptom rating, this approach may mask important details of the greater clinical picture. Individuals at clinical high risk for psychosis (n = 115) were assessed with the SIPS Score Separable Components (SSSC) scale, created to accompany the SIPS positive items by dividing each item into the 7 components identified above. The latent structure of the SSSC was identified with an exploratory factor analysis (EFA). The factors were followed up with validation analyses including hypothesized cognitive, functioning, and symptom measures. Finally, clinical utility analyses were conducted to understand relationships between psychosis risk and common comorbidities. EFA revealed that the SSSC had 3 interpretable factors with the appropriate fit (rmsr = 0.018, TLI = 0.921): Conviction (in-the-moment conviction, retrospective insight), Distress-Impairment (distress, social/role functioning), and Frequency/Duration (frequency, duration). Conviction was minimally valid, Distress-Impairment had excellent validity, and Frequency/Duration was not related to any of the candidate validators. Conviction significantly predicted elevated psychosis risk. Distress-Impairment was related to common comorbid symptoms. Notably, the factors associated more strongly with clinical features than the traditional SIPS scores. The SSSC offers a supplemental approach to single-severity ratings, providing useful clinical insight, mechanistic understanding, and the potential for better capturing heterogeneity in this population.

Sex- and Age-Specific Deviations in Cerebellar Structure and Their Link With Symptom Dimensions and Clinical Outcome in Individuals at Clinical High Risk for Psychosis.

The clinical high-risk (CHR) period offers a temporal window into neurobiological deviations preceding psychosis onset, but little attention has been given to regions outside the cerebrum in large-scale studies of CHR. Recently, the North American Prodrome Longitudinal Study (NAPLS)-2 revealed altered functional connectivity of the cerebello-thalamo-cortical circuitry among individuals at CHR; however, cerebellar morphology remains underinvestigated in this at-risk population, despite growing evidence of its involvement in psychosis. In this multisite study, we analyzed T1-weighted magnetic resonance imaging scans obtained from N = 469 CHR individuals (61% male, ages = 12-36 years) and N = 212 healthy controls (52% male, ages = 12-34 years) from NAPLS-2, with a focus on cerebellar cortex and white matter volumes separately. Symptoms were rated by the Structured Interview for Psychosis-Risk Syndromes (SIPS). The outcome by two-year follow-up was categorized as in-remission, symptomatic, prodromal-progression, or psychotic. General linear models were used for case-control comparisons and tests for volumetric associations with baseline SIPS ratings and clinical outcomes. Cerebellar cortex and white matter volumes differed between the CHR and healthy control groups at baseline, with sex moderating the difference in cortical volumes, and both sex and age moderating the difference in white matter volumes. Baseline ratings for major psychosis-risk dimensions as well as a clinical outcome at follow-up had tissue-specific associations with cerebellar volumes. These findings point to clinically relevant deviations in cerebellar cortex and white matter structures among CHR individuals and highlight the importance of considering the complex interplay between sex and age when studying the neuromaturational substrates of psychosis risk.

Migrant status, clinical symptoms and functional outcome in youth at clinical high risk for psychosis: findings from the NAPLS-3 study.

Migrant status is a known risk factor for psychosis, but the underlying causes of this vulnerability are poorly understood. Recently, studies have begun to explore whether migrant status predicts transition to psychosis in individuals at clinical high risk (CHR) for psychosis. Results, however, have been inconclusive. The present study assessed the impact of migrant status on clinical symptoms and functional outcome in individuals at CHR for psychosis who took part in the NAPLS-3 study. Participants' migrant status was classified as native-born, first-generation, or second-generation migrant. Clinical symptoms were assessed using the Structured Interview for Psychosis-Risk Syndromes (SIPS); functional outcome was measured using the Global Functioning Scales:Social and Role (GF:S; GF:R). Assessments were conducted at baseline, 12-months, 18-months, and 24-months follow-up. Generalized linear mixed models for repeated measures were used to examine changes over time and differences between groups. The overall sample included 710 individuals at CHR for psychosis (54.2% males; Age: M = 18.19; SD = 4.04). A mixed model analysis was conducted, and no significant differences between groups in symptoms or functioning were observed at any time point. Over time, significant improvement in symptoms and functioning was observed within each group. Transition rates did not differ across groups. We discuss potential factors that might explain the lack of group differences. Overall, migrants are a heterogeneous population. Discerning the impact of migration from that of neighborhood ethnic density, social disadvantage or socio-economic status of different ethnic groups could help better understand vulnerability and resilience to psychosis.

Effects of risperidone on psychotic symptoms and cognitive functions in 22q11.2 deletion syndrome: Results from a clinical trial.

Carriers of the 22q11.2 deletion syndrome (22q11DS) have an enhanced risk of developing psychotic disorders. Full-blown psychosis is typically diagnosed by late adolescence/adulthood. However, cognitive decline is already apparent as early as childhood. Recent findings in mice show that antipsychotic medication administered during adolescence has a long-lasting neuroprotective effect. These findings offer promising evidence for implementing preventive treatment in humans at risk for psychosis. We conducted a 12-week double-blind randomized controlled clinical trial with individuals with 22q11DS. Recruitment difficulties resulted in a final sample size of 13 participants (n = 6 treated with antipsychotics and n = 7 receiving placebo). We examined the response to treatment and assessed its short- and long-term effects on psychotic symptomatology using the Structured Interview for Psychosis-Risk Syndromes (SIPS) and cognitive measures. First, two treated participants discontinued treatment after experiencing adverse events. Second, treated participants showed a short-term improvement in 33.3% of the SIPS items, mainly those targeting negative symptoms. Third, reliable improvements in at least one measure of working memory and attention were respectively found in 83.3 and 66.7% of treated participants. This is the first double-blind study to investigate the potential neuroprotective effect of antipsychotics in humans at risk for psychosis. Our preliminary results suggest that antipsychotic treatment may prevent long-term deterioration in clinical symptoms and cognitive skills. Yet, given the limited sample size, our findings need to be replicated in larger samples. To do so, future studies may rather adopt open-label or retrospective designs to ensure sufficient power. [www.ClinicalTrials.gov], identifier [NCT04639960].

Clinical profile and conversion rate to full psychosis in a prospective cohort study of youth affected by autism spectrum disorder and attenuated psychosis syndrome: A preliminary report.

Psychosis can occur at high rates in individuals with autism spectrum disorder (ASD). However, the detection of prodromal psychotic symptoms, including attenuated psychosis syndrome (APS), conditions at high risk of converting to full psychosis, has not been extensively investigated in ASD. We longitudinally evaluate a sample of young ASD individuals (age, mean ± SD: 13 ± 2.9) with (n = 13) or without (n = 18) concomitant APS through a standardized assessment of autistic (Autism Diagnostic Observation Schedule–Second Edition; ADOS−2) and psychotic (Structured Interview for Psychosis-Risk Syndromes, SIPS) symptoms and cognitive and adaptive skills. Individuals with other neuropsychiatric disorders were excluded. We estimated the conversion rate to full psychosis (according to SIPS criteria) over time (39.6 ± 11.5 months) and explored the role of clinical variables at baseline in the transition to full psychosis. A conversion rate to full psychosis of 30.7% was found in ASD/APS. Conversion to full psychosis was not affected by the severity of the autistic and psychotic symptoms. At baseline, young individuals with ASD/APS who later converted to full psychosis showed lower cognitive performance (d = 2.05) and greater impairment of adaptive social functioning profile (d = 1.2) than those with ASD. The results of this preliminary report revealed that nearly a third of young individuals with ASD/APS convert to full psychosis over time. Conversion to full psychosis is affected by decreased cognitive and adaptive skills. Further investigations are needed to confirm the utility of APS detection and to better characterize the psychotic developmental trajectory in ASD, with consequent important implications on prognosis and therapeutic strategies.

Item-level endorsement on the Prodromal Questionnaire in a large non-clinical sample

BackgroundBrief questionnaires, such as the Prodromal Questionnaire (PQ) positive scale, have been used to pre-screen individuals who may be at clinical high-risk (CHR) for psychosis. Despite the apparent utility of the PQ, few studies have examined response styles in non-clinical settings, which this study aimed to assess. MethodsResponse frequencies were examined for PQ positive subscale items in 3584 students (ages 18–35) from a nationally representative, semi-public undergraduate institution. Highly endorsed items were evaluated further in conjunction with established cutoffs and associated symptom ratings from the Structured Interview for Psychosis-risk Syndromes (SIPS) in a smaller subset of participants (n = 162). Positive subscale and distressing item responses were also evaluated by gender, race, and ethnicity using measurement invariance analyses and by comparing the relative proportion of individuals above established cutoffs. ResultsFifteen symptoms were endorsed by over 20 % of the sample with as high as 71 % of respondents endorsing them. Responses to 12 of these items were not associated with ratings on the SIPS. The PQ functioned similarly across demographic characteristics with strong evidence found for gender and race invariance across items and strong ethnicity invariance and partial invariance for positive subscale items and distressing items, respectively. ConclusionsThese findings suggest that a commonly used psychosis-risk questionnaire may not be appropriate for non-clinical samples, with the possibility of high false positive rates of those at CHR for psychosis. Future large-scale epidemiological studies should evaluate if psychosis-risk screeners can be improved to identify CHR individuals in community settings.

Cannabis use and attenuated positive and negative symptoms in youth at clinical high risk for psychosis

Cannabis use is more prevalent among youth at clinical high-risk (CHR) for psychosis than healthy controls (HC). There is mixed evidence as to whether cannabis use is associated with increased severity of attenuated psychotic symptoms (APS) or whether current cannabis use is associated with the transition to psychosis. This study aims to assess cannabis use differences between CHR youth and HC and the impact of cannabis use on APS, clinical status, and transition to psychosis. Participants were from the North American Prodrome Longitudinal Study-3, a prospective longitudinal study including 710 individuals, age 12–30, meeting criteria for a psychosis risk syndrome based on the Structured Interview for Psychosis-Risk Syndromes, and 96 HC. Cannabis use, frequency, and severity of use were assessed with the Alcohol Use Scale/Drug Use Scale. Current and past cannabis use disorders were assessed with the Structured Clinical Interview for DSM-5. Compared to HC, CHR individuals reported significantly increased lifetime cannabis use, during the past six months, and at baseline; greater frequency and severity of cannabis use; and increased prevalence of cannabis use disorder. Relative to CHR youth without cannabis use, CHR cannabis users had significantly higher ratings on baseline grandiosity and lower 12-months social anhedonia. Severity of cannabis was unrelated to clinical status at 2-years, and it did not differentiate CHR individuals who transitioned to psychosis from those who did not. However, a major limitation was that the current number of CHR cannabis users was small, and survival analyses resulted in a smaller power than the 80 % recommended.

Copy number variation at the 22q11.2 locus influences prevalence, severity, and psychiatric impact of sleep disturbance

BackgroundSleep disturbance is common, impairing, and may affect symptomatology in developmental neuropsychiatric disorders. Here, we take a genetics-first approach to study the complex role of sleep in psychopathology. Specifically, we examine severity of sleep disturbance in individuals with a reciprocal copy number variant (CNV) at the 22q11.2 locus and determine sleep’s effect on psychiatric symptoms. CNVs (deletion or duplication) at this locus confer some of the greatest known risks of neuropsychiatric disorders; recent studies suggest the 22q11.2 deletion negatively impacts sleep, but sleep disruption associated with 22q11.2 duplication has not been investigated.MethodsWe compared subjective sleep disturbance and its relationship to psychiatric symptoms cross-sectionally and longitudinally over 1 year in 107 22q11.2 deletion (22qDel) carriers (14.56±8.0 years; 50% male), 42 22q11.2 duplication (22qDup) carriers (16.26±13.1 years; 54.8% male), and 88 age- and sex-matched controls (14.65±7.4 years; 47.1% male). Linear mixed models were used to compare sleep disturbance, assessed via the Structured Interview for Psychosis-Risk Syndromes (SIPS), across groups. Next, CNV carriers were categorized as good or poor sleepers to investigate sleep effects on multiple neurobehavioral traits: psychosis-risk symptoms (SIPS), autism-related behaviors (Repetitive Behavior Scale (RBS) and Social Responsiveness Scale (SRS)), real-world executive function (Behavior Rating Inventory of Executive Function (BRIEF)), and emotional/behavioral problems (Child Behavior Checklist (CBCL)). Linear mixed models tested the effect of sleep category and a group-by-sleep interaction on each measure, cross-sectionally and longitudinally.Results22qDel and 22qDup carriers both reported poorer sleep than controls, but did not differ from each other. Cross-sectionally and longitudinally, poor sleepers scored higher on positive symptoms, anxious/depressed, somatic complaints, thought problems, and aggressive behavior, as well as RBS and SRS total scores. There were significant group-by-sleep interactions for positive symptoms and the majority of CBCL subdomains, in which the difference between good and poor sleepers was larger in 22qDel compared to 22qDup.ConclusionsOur findings indicate that CNVs at the 22q11.2 locus impact sleep which, in turn, influences psychopathology. Sleep disturbances can differentially impact psychopathology, depending on 22q11.2 gene dosage. Our findings serve as a starting point for exploring a genetic basis for sleep disturbance in developmental neuropsychiatric disorders.